Insect repellents



Patented Sept. 3,19146 UNITED STATES PATENT OFFICE.v

INSECT REPELLENTS 7 Benjamin G. Wilkes, Wilkinsburg, Pa., aasignor toCarbide and Carbon Chemicals Corporation, a v corporation of New York NoDrawing. Application February 11, 1043,

Scrial No. 475,566

Many and varied have been the expedients to which people have resortedfrom time to time in attempting to protect themselves from biting andblood sucking insect pests, and substances which repel the insects anddiscourage biting by these pests constitute one of the importantprotections for health and comfort. The efi'ectiveness of oil ofcitronella, widely known as a repellent, was reported as early as' 1901,and prior to and since that time many other essential oils, mixtures ofvarious kinds of oils, greases and ointments and powders have been triedwith various degrees of success.

A substance to be generally acceptable as a repellent should possessdurability or effectiveness over arelatively long period of time againstone or more of such biting or blood sucking pests as mosquitoes, flies,fleas, chiggers and the like. To this end it should be relatively stablechem ically, and not readily dissipated by evaporation or vaporization,although it is believed'that at least some degree of volatilityisessential. For dermal application, a repellent should be nonirritatingand easy to apply with the hands or a swab. For use under wet-skinconditions, that is, skin which may be moist or wet as by perspiration,the repellent preferably should be relatively insoluble in water.

Repellents which may afiect clothing by staining, bleaching or weakeningof the fiber, or which 30 leave an objectionable oily appearance or feelon the skin are limited in their usefulness. Preferably, the repellentshould be free of odor, especially such odors as may be regarded asunpleasant or disagreeable, and diflicult to mask. Preferably, also, therepellent substance should have little or no solvent action on variousfinishes, paints, varnishes, lacquers and the like.

I have found that the desirable qualities or characteristics enumeratedabove, as well as excellent repellent activity, are combined to anexceptionally high degree in relatively non-volatile organic compounds,containing carbon, hydrogen and oxygen, in which two oxygen atoms'arepresent in alcoholic hydroxyl groups attached to different carbon atoms,and the carbon and oxygen are present in a ratio of more than two carbonatoms for each oxygen atom. The compounds with which this invention ismore particularly concerned contain not les than seven carbon 50 atomsto the molecule with not more than four carbon atoms separating eachhydroxyl group from the nearest oxygen atom, with the number of carbonatoms in the chain directly connecting 8 Claims. (Cl. 167-22) 2 two lessthan the total number or carbon atoms in the molecule and not exceedingseven. In general, these compounds, chemically classified as diols, havebeen found to have boiling points between 85 C. and 160 C. at anabsolute pressure of about 3 to 7 millimeters of mercury, andparticularly good results have been obtained with diols distillingbetween 95 to 150 C. at 5 mm. pressure, equivalent approximately to arange of 80 C. to 135 C. at 2.0 mm. pressure. Especially useful diolsare those which are free of carbonyl oxygen atoms, i. e. having nooxygenatom attached by more than one bond to the same'carbon atom.

The repellent diols are for the most part liquids, at ordinarytemperatures, which have but a limited miscibility with water and whichmay be placed directly in contact with the skin without substantialirritant effect. Where thesensitivity or the skin to irritants is apredominant factor the lower molecular weight members may, in general,be more suitable. The appearance or feel when first applied in aneffective amount is not unduly oily and,,within a short time becomes 5practically unnoticeable. The odor, if any, is mild and may be readilymasked. The solvent action on materials or articles with which the diolsare likely to 'come' in contact during ordinary use is slight, andfabrics, paints, varnishes, lacquers, plastics and the like are notappreciably attacked by them, if'at all. 4

These repellent diols afford relatively lasting protection against oneor more of such biting and blood sucking pestsas: fresh watermosquitoes, Aedes hirsuteron, Aedes stimulans, Aedes aeylmti, Anophelesquadrimaculatus, Aedes triseriatus, Culer pipens, Aedes trivittatus, andAedes verans; salt marsh mosquitoes, Ae-de's sollicitans, Aedescanister, and Aedes iaem'orhynchus; black files,

40 Simulium spp.; sand flies, Culicoides spp.; stable flies, Stomoryscalcitmns; deer flies, Chrysops spa; cat fleas, Ctenocephalides felts;dog fleas, Ctenocephalides canis; stick tight ileas, Echidnophagagallinaces; and chiggers or red bugs, Trombicula spp.

The protection against mosquitoes which is afforded by the repellents ofthe present invention is superior to that given by oil of citronella, asmeasured according to the method for comparing repellent efiectivenesswhich is described in the Journal of Economic Entomology, volume 33, pp.563 and 566, July 20, 1940. The substance to be tested is applied to anarm from wrist to elbow or a leg from ankle to knee and the area thusthe two alcoholic hydroxyl groups being atleast treated exposed toattack. In determining the protection aiforded by the substance, thetime in minutes to the first bite on the treated area may be designateda the repellent protection time for that substance. During the time ofthe test the insect activity is determined by observation of the bitingfrequency (bites per minute) on corresponding untreated areas as acontrol. As might be expected, the repellent protection time for a givensubstance is not the same for diilerent biting frequencies but decreaseswith an increase in biting rate on untreated areas. Comparative tests ona number of repellents have shown that for a given pair of repellentsthe ratio of their repellent protection times at the same bitingfrequency may be taken to be approximately constant over the entirerange of-biting frequency on corresponding untreated areas. This ratiomay be designated the average repellency rating of a repellent withrespect to a given standard, and the ratings given herein are on thebasis of oil of citronella=100.

In general, the diols of the present invention are from about one toupwards of seventimes as efiective as oil of citronella against aparticular insect for biting frequencies over a range from about 0.4 to40 bites per minute, average, on corresponding untreated areas.

Within the above defined class of substances with which this inventionis broadly concerned, saturated 1,2-diols and 1,3-diols composed ofcarbon, hydrogen and only two oxygen atoms to the molecule arepreferred. These 1,2- and 1.3-diols may be regarded as substitutionproducts of ethylene glycol and trimethylene glycol (l,3-propyleneglycol) in which one or more of the hydrogen atoms attached to thecarbon atoms are replaced by a corresponding number of hydrocarbonradicals, as represented by the following formula: A(OH):, in which A isa saturated hydrocarbon radical having from seven to sixteen carbonatoms, including an open chain of from two to three aliphatic carbonatoms, and in which the hydroxyl groups are alcoholic and attached todifferent carbon atoms in said chain.

It has been found by test that, in addition to being superior repellentsfor ordinary use, the eflectiveness of these preferred diols is goodeven under severe conditionsof service. For instance, they are efiectiverepellents on the moist or wet skin met with under such conditions ashigh humidity and profuse perspiration resulting from physical activity,although it may be necessary to repeat the treatment more frequentlythan upon a dry skin for equivalent results. Furthermore it is difilcultto remove these diols from the treated area, to an extentsufiicient toeliminate completely their repellent eil'ect, by rubbing or brushingwith clothing or such other material or substances as are likely to comein contact with the skin, for instance grass, weeds, leaves, bushes,itliies and other vegetation, dirt, sand and the Specific 1,2- and1,3-diols which are useful as insect repellents include:

2-ethylhexanediol-l,3

3,5-diniethylhexanediol-2,3

6-methylheptanediol-2,4

3-methyloctanediol-2,3

2-ethyl-2-methylolhexanol-1 (2 ethyl-2 butylpropanediol-l,3)

2-butyloctanediol-L3 2,2,4-trimethylpentanediol-1,3

2-amylnonanedioi-1,3

2- l-hydroxyethyl) cyclohexanol 4 The invention may be furtherillustrated by the following examples:

Exams 1 cmon cmcmba cmcmcmcaon z-ethylhexanedicl-La (2-ethvl-3-Pmlvrmnedtol-m) 2-ethylhexanediol-1,3 was applied to a forearm, fromwrist to elbow, in an amount providing 0.01 milliliter of substance persquare inch of skin surface, the other forearm being untreated. Everyone half hour to one hour over the test period, the treated surface andthe untreated surface were exposed for about one to two minutes in atest cage (30 x 30 x 30 inches) containing from 500 to 1000 mosquitoes,of which about one half were females. The first bite on the treatedsurface determined the end of the test period. The temperature wasmaintained at 75 to 78 F. and the relative humidity about to per cent.An average of seven tests on the undiluted material over a range ofbiting frequencies from 10 to 40 bites per minute, average, on theuntreated area, gave an effective repellency rating of at least 500against Aedes aewpti.

A series of field tests which gave a ratingof about 580 against saltmarsh mosquitoes, mainly Aedes sollicitans, were carried out inthevicinity of Barnegat, N. J. In these field tests the 2-ethylhexanediol-1,3 was applied to the arm from wrist to elbow and tothe leg from ankle to knee in amounts providing 0.01 milliliter persquare inch. The treated areas were exposed continuouslyand theuntreated area was exposed every half hour for a period of two minutes,as a control. The average number of bites per minute on the untreatedarea ranged from 4 to 27. A temperature between 74 to 92 -F. and arelative humidity of about 50 to percent prevailed throughout the tests.Tests on deer flies, Chrysops spp. and stable flies or dog flies,Stomosus calcitrans showed that they were repelled for about one half tothree fourths of the time that the treated surfaces were protectedagainst the mosquitoes.

Additional field tests against upland swamp mosquitoes, mainly Aedestrivittatus and some Aedes vexans, in the vicinity of Chatham, N. J.,

gave an average value of about 790 for the effective repellency rating.The temperature was about to 84 F. with a relative humidity about 50 to60 percent and the average number of bites on the untreated area rangedfrom about 15 to 28 per minute. Otherwise the tests were carried out inthe same manner as the field tests against the salt marsh mosquitoes.

On various dilutions up to about 70 percent of the diluent, by volume,with various compatible carrier substances, the eflective repellencyrating of the compositions were found on the whole to be slightly higherthan corresponded to the dilution of the repellent substance present.This was the case with such diluents as ethanol, isopropanol,monopropylene glycol, castor oil, vanishing cream and the like.

2-ethylhexanediol-L3 was found to evaporate only slowly when spreadthinly over relatively large areas. For instance, slightly less than0.01 gm. spread over about 13 square inches of a ground glass plateevaporated only about 12 percent in 24 hours at a room temperature ofabout 74' IE. and about 50 to 60 percent in 24 hours on heating theplate to a temperature of about 94 to 96' 1c. the room conditionsotherwise remaining the same.

Extended ileld tests with a group oi. subjects under wet skin conditionswere also carried out in a grove in'Florida where Aedes taeniorhimchuswere abundant. During the course of the tests the subjects engaged inmoderate physical activity with care being taken to prevent the treatedsurfaces from coming into rubbing contact with clothing. vegetation andthe like. The temperature and humidity were sufliciently high to causethe subjects to perspire freely, with consequent wetting of the treatedskin area. Th average repellency rating againstAedes taeniorhzmchus inthese tests was about 520.

A more severe type of test was also carried out under substantially thesame conditions. In

these tests attempts were made to rub oil! or brush on the repellentabout 30 minutes after it had been applied. The test subjects walkedthrough grasses and weeds about shoulder high and tried to rub therepellent from treated arm and leg areas. Handfuls of vegetation wereused as brushes and the treated areas were rubbed vigorously. In someinstances the subjects were on the ground in contact with the dirt andin others the treated areas were rubbedthoroughly on the clothing of thesubject or with a paper towel. It was found that under rubofi conditionsthe repellent must be applied more frequentlythan under normalconditions, for equivalent protection. On the average the time until thefirst bite was received was reduced to about two hours under ruboflconditions, amounting to a reduction of about four hours.

2-ethylhexanediol-1,3 as used is a slightly oily liquid distilling at2442 C. at 760 mm.; at 163 C. at 50 mm.; at 129 C. at mm. and 102 C. at3 mm. of mercury absolute pressure. Its vapor pressure at C. was lessthan 0.01 mm. of mercury and it had a gravity of 0.9422 (20/20 C.) Itsabsolute viscosity was 271 centipoises and solubility in water was 016percent by weight, both at 20 C. At the same temperature water wassoluble in it-to 10.8 percent by weight. 2-ethylhexanedlol-1,3 was foundto be physiologically safe under the conditions of use for which it isintended.

EXAMPLE 2 was found to have an effective repellency rating above 590against captive Aedes aegz pti.

Similar tests'on propanediol-1,3 distilling at 214 C. at 700 mm. gave avalue for the repellency rating of about 9 am 1st captive Aedes aewpti,by way of comparison.

CHIOHOH Hi (CBOsGHsOHsHOH d-methilMtanedioi-ZA (1-methyl-3-isobutylpropanediol-1,3)

The repellency rating of 6-methylheptanedisl- 2,4 which was a ratherviscous liquid distilling at 9344 C. at 3 mm. pressure (about 105 C. at5 mm.) was found to be 593 against captive Aedes aewpti. This rating isto be compared with an 111 C. at 21 mm. pressure (about 84 C. at 5 mm.)was found to have an effective repellency :rating of about 120 againstcaptive Aedes aem pti. It boils substantially below the2-ethylhexanediol-1,3 of Example 1.

Exams: 6

H on

Cs u I OH CH: 3-methyloctcnediol-2,3 (2-pent1/lbutanediol-2,3)

3-methyloctanediol-2,3 distilling at 94 C. at 3 mm. pressure (107 C. atabout 5 mm.) was found to have a rating of about 470 against captiveAedes aegypti. This substance is somewhat higher boiling than the 3,5dimethylhexanediol- 2,3 of the preceding example and had a slight, notunpleasant odor. It was observed also that the mosquitoes did not lighton the treated areas up to the time of the first bite.

For purposes of comparison, similar repellency tests against captiveAedes aegypti were made with butane diol-2,3 distilling at 184 C. at 760mm. and 2-methylbutanediol-2,3 distilling at 83 C. at 20 mm. pressure(68 C. at 5 1pm.). ratings were found to be about 25 and 30,respectively.

EXAHI'LE 7 H(0Ca sCHs)sOH Tripropylene glycol I Tests on tripropyleneglycol distilling at 111 C. at 3 mm. pressure (about 126 C. at 5 mm.)gave a rating of about 250 against captive Aedes aeaypti.

- Tests on triethyleneglycol distilling at 288 .C. at 760 mm. (144 C. at5 mm.) gave a rating of 49 against captive Aedes aegypti under similarconditions, for purpose of comparison.

7 mint:

CEiCHQ CHiCHaOH (cm), on

2-methulpentanediol-2,4 monoe thylene glycol ether The monoethyleneglycol 'ether of 2-methylpentanediol-2,4 distilling at 90 C. at 2.5 mm.

(102 C. at 5 mm.) was iound to have a rating of about 870 againstcaptive Aedes aeazmti.

ExAMPLs 9 CBICHO Ct |O CIHIOH Hi (CHIhOH 2-methylpentanediol-2,4diethylene glycol other The diethylene glycol ether of 2-methylpen-'tanediol-2,4 distilling at 110 C. at 2.5 mm. pressure (123 C. at 5 mm.)was found to have a rating of about 360 against captive Aedes aegypti.

EXAMPLE 10 H CH3): 0 C:H|(CH|) OH H! 011016011 Z-methylpantanediol-ZAmonopromllene glycol ether The repellency rating of the monopropyleneglycol ether of 2-methylpentanediol-2,4 distilling at 108 C.-114 C. at 9mm. pressure (about 99 C. at 5 mm.) was found to be about. 480 againstcaptive Aedes aegypti.

EXAMPLE 11 2-methylpentanediol-2,4 dipropylene glycol ether Thedipropylene glycol ether oi. 2-methylpentanediol-2,4 distilling at122-128 C. at 8 mm. pressure (about 119 C. at 5 mm.) was found to have arepellency rating of about 550 against 0 a repellency rating of about250 against captive Aedes aegypti.

EXAMPLE 13 CH:0C:H|(CH|)OH ClHlCH c1111 HOH Z-ethylhezanediol-IJmonopromllene glycol ether The monopropylene glycol ether of2-ethylhexmedial-1,3 distilling at 112 C. at 2 mm. pressure (about 131C. at 5 mm.) was found to have a repellency rating of about 370 againstcaptive Aedes aemmti.

Various modifications of the invention will be appail-ent within thescope of the appended claims.

I c aim:

1. A method of repelling insects which includes applying to a zone to betreated an insect repellent comprising as an essential repellentingredient thereof an organic diol distilling between C. to C. at anabsolute pressure of about 5 millimeters of mercury, carbon and oxygenbeing present in a ratio of more than two carbon atoms for each oxygenatom; said diol containing not less than seven carbon atoms to themolecule with the hydroxyl groups of said diol attached to diilerentcarbon atoms in an open chain and not more than four carbon atomsseparating each hydroxyl group from the nearest oxygen atom; the totalnumber of carbon atoms in the chain directly connecting the twoalcoholic hydroxyl groups being at least two less than the total numberof carbon atoms in the molecule and not exceeding seven. 2. A method ofrepelling insects which includes applying to a zone to be treated aninsect repellent comprising as an essential repellent ingredient thereofa saturated aliphatic diol in which carbon and oxygen are present in aratio. of more than two carbon atoms for each oxygen atom; said diolcontaining from seven to sixteen carbon atoms to the molecule with thehydroxyl groups of said diol attached to different carbon atoms in anopen chain and not more than four carbon atoms separating each hydroxylfrom the nearest oxygen atom; the total number of carbon atoms in thechain which directly connects the alcoholic hydroxyl groups being atleast two less than the total number of carbon atoms in the molecule andnot exceeding seven.

3. A method of repelling insects which includes applying to a zone to betreated an insect repellent comprising as an essentialrepellentingredient thereof a saturated aliphatic diol distillingbetween 95 C. and 150 C. at an absolute pressure of about 5 millimetersof mercury, carbon and oxygen being present in a ratio of more than twocarbon atoms for each oxygen atom; said diol containing from seven tosixteen carbon atoms to the molecule with the hydroxyl groups of saiddiol attached to different carbon atoms in an open chain and not morethan four carbon atoms separating each hydroxyl from the nearest oxygenatom; the total number of carbon atoms in the chain which directlyconnects the alcoholic hydroxyl groups being at least two less than thetotal number of carbon atoms in the molecule and not exceeding seven.

- 4. A method of repelling insects which includes applying to a zone tobe treated an insect repellent comprising as an essential repellentingredient thereof a diol of the general formula A(OH)2' in which A is asaturated aliphatic hydrocarbon radical having from seven to sixteencarbon atoms, including an open chain of from two to three carbon atoms,and in which the hydroxyl groups are alcoholic and attached to diflerentcarbon atoms in said chain.

5. A method of repelling insects which includes applying to a zone to betreated an insect repellent comprising as an essential repellentingredient thereof an open chain alkane diol containing from seven tosixteen carbon atoms to the molecule and distilling between 95 C. and150 C.

at an absolute pressure of about 5 millimeters of applying to a zone tobe treated an insect repellent comprisingas an essential repellentingredient thereof an octane diol in which the alcoholic 8. A method ofrepelling insects which includes 10 v 10 applying to a zone to betreated an insect repellent composition comprising as an essentialrepellent ingredient thereof an open chain alkane diol containing fromseven to sixteen carbon atoms to the molecule and distilling between 95C. and 150 C. at an absolute pressure of about 5 millimeters of mercuryin whichthe alcoholic hydroxyl groups are attached to adjacent carbonatoms.

BENJAMIN G. WILKES.

